Grosse Gerrit M, Derda Anselm A, Stauss Ricarda D, Neubert Lavinia, Jonigk Danny D, Kühnel Mark P, Gabriel Maria M, Schuppner Ramona, Wilhelmi Mathias, Bär Christian, Bauersachs Johann, Schrimpf Claudia, Thum Thomas, Weissenborn Karin
Department of Neurology, Hannover Medical School, Hannover, Germany.
Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
Front Neurol. 2021 Nov 24;12:755827. doi: 10.3389/fneur.2021.755827. eCollection 2021.
Specific microRNAs (miRs) have been implicated in the pathophysiology of atherosclerosis and may represent interesting diagnostic and therapeutic targets in carotid stenosis. We hypothesized that the levels of specific circulating miRs are altered in patients with symptomatic carotid stenosis (sCS) in comparison to those in patients with asymptomatic carotid stenosis (aCS) planned to undergo carotid endarterectomy (CEA). We also studied whether miR levels are associated with plaque vulnerability and stability over time after CEA. Circulating levels of vascular-enriched miR-92a, miR-126, miR-143, miR-145, miR-155, miR-210, miR-221, miR-222, and miR-342-3p were determined in 21 patients with sCS and 23 patients with aCS before CEA and at a 90-day follow-up. Transcranial Doppler ultrasound for detection of microembolic signals (MES) in the ipsilateral middle cerebral artery was performed prior to CEA. Carotid plaques were histologically analyzed. Mean levels of miRs were not considerably different between groups and were only marginally higher in sCS than aCS concerning miR-92a, miR-210, miR-145, and miR-143 with the best evidence concerning miR-92a. After adjustment for vascular risk factors and statin pre-treatment, the effect sizes remained essentially unchanged. At follow-up, however, these modest differences remained uncorroborated. There were no relevant associations between miR-levels and MES or histological plaque vulnerability features. This study does not provide evidence for strong associations between specific circulating miRs and symptomatic state in a collective of comprehensively characterized patients with carotid stenosis. Further work is needed to elucidate the role of circulating miRs as targets in advanced carotid atherosclerosis.
特定的微小RNA(miR)已被认为与动脉粥样硬化的病理生理学有关,可能是颈动脉狭窄中有趣的诊断和治疗靶点。我们假设,与计划接受颈动脉内膜切除术(CEA)的无症状颈动脉狭窄(aCS)患者相比,有症状颈动脉狭窄(sCS)患者的特定循环miR水平会发生改变。我们还研究了CEA术后miR水平是否随时间与斑块易损性和稳定性相关。在21例sCS患者和23例aCS患者CEA术前及90天随访时,测定了血管富集的miR-92a、miR-126、miR-143、miR-145、miR-155、miR-210、miR-221、miR-222和miR-342-3p的循环水平。CEA术前进行经颅多普勒超声检查,以检测同侧大脑中动脉的微栓子信号(MES)。对颈动脉斑块进行组织学分析。两组间miR的平均水平差异不大,仅在miR-92a、miR-210、miR-145和miR-143方面,sCS组略高于aCS组,其中miR-92a的证据最为充分。在调整血管危险因素和他汀类药物预处理后,效应大小基本保持不变。然而,在随访时,这些微小差异并未得到证实。miR水平与MES或组织学斑块易损性特征之间无显著相关性。本研究未提供证据表明在一组全面特征化的颈动脉狭窄患者中,特定循环miR与症状状态之间存在强关联。需要进一步开展工作以阐明循环miR作为晚期颈动脉粥样硬化靶点的作用。